Menu
GeneBe

SARS1

seryl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:109213917-109238182

Previous symbols: [ "SARS" ]

Links

ENSG00000031698NCBI:6301OMIM:607529HGNC:10537Uniprot:P49591AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
  • neurodevelopmental disorder with microcephaly, ataxia, and seizures (Moderate), mode of inheritance: AR
  • neurodevelopmental disorder with microcephaly, ataxia, and seizures (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Neurodevelopmental disorder with microcephaly, ataxia, and seizuresARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic28236339

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARS1 gene.

  • not provided (9 variants)
  • Neurodevelopmental disorder with microcephaly, ataxia, and seizures (4 variants)
  • Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome (2 variants)
  • Inborn genetic diseases (2 variants)
  • SARS1-related disorders (1 variants)
  • Cerebral arteriovenous malformation (1 variants)
  • See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
3
clinvar
1
clinvar
5
missense
1
clinvar
1
clinvar
3
clinvar
1
clinvar
6
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
2
3
non coding
2
clinvar
2
Total 2 1 4 4 3

Variants in SARS1

This is a list of pathogenic ClinVar variants found in the SARS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-109214040-A-G SARS1-related condition Likely benign (Apr 15, 2019)3057588
1-109214083-G-A not specified Uncertain significance (Oct 27, 2022)3157852
1-109214096-A-G not specified Uncertain significance (Nov 01, 2022)3157843
1-109214118-G-A See cases Uncertain significance (Oct 06, 2021)1690455
1-109228386-C-T not specified Uncertain significance (Jun 01, 2023)2555194
1-109228424-G-A not specified Likely benign (Apr 14, 2022)3157847
1-109228441-T-C Neurodevelopmental disorder with microcephaly, ataxia, and seizures Benign (Nov 07, 2021)1327978
1-109229463-C-G not specified Uncertain significance (Dec 21, 2022)3157848
1-109229480-G-A not specified Uncertain significance (Nov 06, 2023)3157849
1-109229487-G-A SARS1-related condition Uncertain significance (Oct 25, 2023)3061594
1-109229572-G-A Benign (Dec 31, 2019)767683
1-109230915-G-A not specified Uncertain significance (Aug 16, 2021)3157850
1-109230944-G-A Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic (Jul 01, 2022)440921
1-109231677-G-T Neurodevelopmental disorder with microcephaly, ataxia, and seizures Likely pathogenic (-)1209576
1-109235318-C-T not specified Uncertain significance (Apr 07, 2022)3157851
1-109235353-G-T SARS1-related condition Likely benign (Dec 31, 2019)714605
1-109235366-C-T Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic (Apr 19, 2023)2499499
1-109235412-G-A Neurodevelopmental disorder with microcephaly, ataxia, and seizures Uncertain significance (Apr 27, 2019)638324
1-109235430-AGGT-A SARS1-related disorders Pathogenic (Apr 27, 2023)2443972
1-109235955-T-C Neurodevelopmental disorder with microcephaly, ataxia, and seizures Benign (Nov 07, 2021)1327979
1-109235978-T-C Cerebral arteriovenous malformation Pathogenic (Feb 14, 2018)545102
1-109236048-C-T Likely benign (Jan 30, 2018)721604
1-109236451-G-A Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome Benign/Likely benign (Nov 01, 2023)774395
1-109236459-C-T Neurodevelopmental disorder with microcephaly, ataxia, and seizures Pathogenic (Apr 19, 2023)2499500
1-109236487-C-T Neurodevelopmental disorder with microcephaly, ataxia, and seizures • not specified Uncertain significance (Apr 27, 2022)2506443

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SARS1protein_codingprotein_codingENST00000234677 1124252
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9990.000749125744031257470.0000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.661702990.5680.00001703378
Missense in Polyphen36114.750.313721309
Synonymous1.48941140.8230.00000639973
Loss of Function4.70229.60.06750.00000175321

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.;
Disease
DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Aminoacyl-tRNA biosynthesis - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);tRNA Aminoacylation;Translation;Selenocysteine synthesis;Metabolism of proteins;Metabolism of amino acids and derivatives;Glycine Serine metabolism;selenocysteine biosynthesis;Metabolism;tRNA charging;Selenoamino acid metabolism;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

pRec
0.261

Intolerance Scores

loftool
0.145
rvis_EVS
-0.32
rvis_percentile_EVS
31.69

Haploinsufficiency Scores

pHI
0.190
hipred
Y
hipred_score
0.749
ghis
0.547

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sars
Phenotype

Zebrafish Information Network

Gene name
sars
Affected structure
trunk vasculature
Phenotype tag
abnormal
Phenotype quality
branchiness

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;translation;tRNA aminoacylation for protein translation;seryl-tRNA aminoacylation;tRNA processing;selenocysteine metabolic process;negative regulation of angiogenesis;selenocysteinyl-tRNA(Sec) biosynthetic process;negative regulation of vascular endothelial growth factor production
Cellular component
nucleus;cytoplasm;cytosol;extracellular exosome
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;RNA binding;serine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;selenocysteine-tRNA ligase activity